How to develop an eTMF automation strategy
Over the past 10 years, the Trial Master File, or TMF, has transformed into a powerful and digital “Single Record of Truth” known as the eTMF. This transformation is the result of global industry collaboration, including the establishment of the TMF reference model.
But an eTMF is not a clinical trial automation solution. Think of it more like a highly organized electronic file cabinet. When we talk about eTMF automation, we are talking about automating all the manual processes that move essential documents back and forth between the trial sponsor and the site investigators. The eTMF is the final resting place for all those documents.
Each essential document has specific requirements for sending, receiving, acknowledging, collaborating, signing and storing. Moving those documents back and forth using postal mail, fax machines, or email messages is not automation. No matter how efficient your manual processes might be, it takes a lot of human effort to keep essential documents organized during a trial.
To truly automate an eTMF, a sponsor must commit to a paperless system for essential document collaboration and archiving. The following are the four most common automation strategies.
There are a number of strategies for automating the flow of documents from study start-up to study closeout. The following is a list of eTMF automation strategies we have observed by meeting with clinical research organizations:
- Wait and see if our eTMF vendor develops an automation product in the future
- Build In-house software customized to meet our company’s specific needs
- Contract with a large consulting company to lead the project and develop a solution
- Organize a project team to evaluate commercial software solutions
The strategy your organization chooses depends on a number of factors. For example, waiting to see if new automation solutions are delivered by your eTMF vendor would postpone your decision today, but it won’t help you solve challenging compliance hurdles that are trending toward more auditing of essential document compliance in eTMFs and ITMFs.
Building in-house software has some advantages, including more control over the software requirements and eventual ownership of a finished system without the need of a software vendor. But a disadvantage to this approach is that it could end up costing more money than commercial software and not provide the same product maturity a commercial product can provide.
Organizing a team to evaluate commercial software solutions is a great strategy for a number of reasons. First of all, by watching a demonstration of commercial software, you gain insight into the dozens of ideas that previous clinical trial sponsors added to the product over the years. Secondly, you can view commercial software as a viable alternative to any other strategy if the product can save your organization money, improve your service level to sites, and organize the flow of documents to be audit ready at all times.
Even if your organization is determined to build custom software, a deep dive into a commercial version can help clarify your technical teams understanding of the project they are taking on.
The following are some examples of automation goals. These goals are important because they support the business case of the project.
To complete a transformation to a paperless system must address clinical trial collaboration challenges between sponsor and site, and where possible, automated. The following 5 goals are examples that have value to our customers, your organization may have different goals or additional goals.
- Digitize clinical processes with sites, to increase trial productivity and document quality.
- Track site documents in real time throughout the study lifecycle
- Understand the optimal use of human resources during a trial
- Give eTMF owners visibility into completeness gaps
- Enable real-time quality checks that ensure inspection readiness
CHALLENGES TO AUTOMATION
There are lots of challenges to complete automation. It is important to articulate as many of these challenges as you can gather from project stakeholders.
- Site-specific, country-specific, regulatory specific “document workflows” must be included
- CRA’s should become “Cultural change agents” and show site investigators the better way
- Global harmonization of disparate local processes
- Establish a cross functional team to ensure success of the project
There is no doubt that every large organization needs an eTMF automation strategy. There is no way to stay in control of hundreds of thousands of eTMF artifacts without automating the flow of essential documents on their way from sponsor to site, and from site to sponsor.
At InnovoCommerce we believe every organization should review our product in their conference room. Regardless of which strategy you choose, a deep dive into our commercial software will give your team the clarity they need to make an eTMF automation decision.
Frequently Asked Questions about eTMF Automation
How can we truly go paperless if trial sites prefer wet signatures?
The short answer is that you don’t have to force sites to go paperless. We have found that tens of thousands of users at sites using our Study Collaboration Portal software were thrilled to go paperless, including eSignature, once they logged in to the portal and saw that it supported both wet signature and eSignature.
There is always a bit of cultural change required when technology advances. But in this case, our customers learned sites become the biggest advocates once they experience how much time can be saved by moving away from wet signatures. However, when sites do execute wet signatures, our software sends that document with its wet signature into a special QC check. Once the wet signature is approved, that document and its wet signature continue to move along as a paperless document.
Do you have any stats on how long it takes for a document in your system to go from site collaboration and collection to eTMF?
During paper-based trials, essential documents can take 40 to 60 days from scan until final QC check, prior to adding them to your eTMF system. Our Study Collaboration Portal solution eliminates all the paper-based steps, including printing, signing, scanning, and scan inspections. That means when a document is distributed by our system, depending on whether or not it needs a signature, the document is ready for a final QC immediately or upon eSignature a few days later. This process includes the documents collected from the Sites. The eTMF can receive documents immediately after a single QC review. Timeliness and contemporaneousness become the default status of your eTMF.
How much time does a CRA need to spend in your system to review the site binder during a monitoring visit?
Because Study Collaboration Portal is automated and paperless, completeness is decoupled from site monitoring visits. There is never a reason to check the binder at a site because the binder can no longer be out of order, it wont be missing an artifact, and it can’t contain an outdated document. Site Binders are always in a state of completeness.
If a site needs to sign or acknowledge anything, the sponsor is already aware of the missing signature or acknowledgment without a site visit. And the site is aware of their incomplete task because it is the first thing they see when they log in. For these reasons, CRAs can spend time at the sites doing more productive things than reviewing paper binders.
Does your system send out a lot of emails to sites? Don’t paperless systems send out way too many reminders upon reminders?
Our customers usually set up Study Collaboration Portal to send once per week digest emails that contain clickable links to any actions that need to be taken care of. This strategy not only solves the issue of getting too much email, but it also gives sites a chance to get their work done without getting reminders from a system that doesn’t know whether the site already took care of a task. When we launched “Digest” messaging in version 6 of the Study Collaboration Portal, our site user productivity increased, and task cycle time dropped. It is a good balance between harping on users and helping users complete their work.
Study Startup has a lot of sub-processes. How does your software deal deal with the complexity of distributing and collecting the variety of startup documents?
A recent ACRP article on study startup said it best, “a large chunk of start-up effort is spent on coordinating the essential document compilation, review and reconciliation steps required for various submission packages”. Automating startup essential document workflow is complicated because there are 8 different essential workflows in every study and a study startup package contains at least 4 of them.
This is exactly where Study Collaboration Portal provides maximum benefit and efficiency. Our purpose built workflows are automated and they require no configuration as they route correctly, right out of the box. From trial start to trial finish, Study Collaboration Portal eliminates the study startup paper ISF, and manages a paperless compilation and automated distribution of the package as it tracks the package status in real-time until completed.
How can we effectively track and approve the Informed Consent that is being edited by the site prior to site startup?
The collaboration workflow built into the Study Collaboration Portal enables the site to edit the Informed Consent provided by the sponsor and send it back to the sponsor for approval. The sponsor can provide feedback or approve the document. Once the document is approved, it is locked and cannot be edited. The site can then submit the document for IRB/EC approval, provide IRB/EC feedback to sponsor and finally upload the IRB/EC approval letter back to Study Collaboration Portal. All versions of the Informed Consent along with changes made at every stage are maintained in an audit trail.
How do you handle the Closeout document collection process?
During the closeout process, all study files are reconciled with the Trial Master File. This used to be a painstaking and time-consuming process. However, Study Collaboration Portal has completely automated this process by designing a system that keeps essential documents validated at all times and transferred to the eTMF for QC in real-time. However, any missing document, such as study team licenses, CV’s, laboratory documentation, etc. will be available as an open task for the site to complete.
The CRA can simply monitor everything remotely during the trial to ensure the site completes all required documentation in a timely manner, long before closeout. Once a site’s role in the trial is complete, the sponsor has the ability, in one click, to archive all documents and communication provided to the site during the conduct of the study and provide that archive to the site. All documents and correspondence are automatically converted to PDF for long term retention by the site.
Why should I consider InnovoCommerce over [fill-in-the-blank]?
We don’t mess around when it comes to designing and building great software. We have been delivering enterprise scale software for drug safety, device complaint handling and clinical trials since 1995. Our team envisioned the Argus Safety product in 1996 and launched it to the world in 1998. (At a time when there were many other companies already offering software for adverse event handling.)
Today, Study Collaboration Portal is the only commercial software to deliver end-to-end automation of regulatory document distribution and exchange from study startup to study close out. Our customers are years ahead of their competition by using our product.
You can count on us to deliver a scalable enterprise solution to your trial document challenge, You don’t have to build your own. Contact us for a demonstration today.
Can you validate our installation?
Sure can! We can provide a spectrum of go-live support from supplying baseline validation templates to designing and executing your validation scripts for you. Every deployment starts with a set of project templates and other standard artifacts like administration guides, validation guides, and a functional design specification. Then we work with customers through pilots to identify gaps and find what they need to get the system up and running. Contact us for more information on deploying SCP at your organization..
Novo Nordisk and Boehringer Ingelheim have automated the distribution and collection of regulatory documents from study startup to study closeout. We asked both companies to make the business case for paperless essential document workflow. Their feedback inspired this article: “The Top 10 Reasons to Automate Your Essential Documents.”
(Both Novo Nordisk and
Boehringer Ingelheim use software from InnovoCommerce to automate
their regulatory document workflow)
#1 – Update study documents faster
It is always faster to
update a digital document than a paper document. Consider the time it
takes to print an update to a study protocol, insert
the update into the protocol while archiving the old version, and documenting
those changes in an audit trail. Sponsor study teams and site staff could spend
an hour on a task that would have taken 10 seconds in a
paperless trial. Keep in mind that in this example, over the course
of a Study, the Protocol gets amended multiple times. So, going paperless has
an absolute speed advantage over paper.
#2 – Retire old document versions automatically
When you hold two paper
versions of the same document in your hand, it can be difficult to
identify which document includes the latest changes. During a clinical
trial, paperless systems retire old documents as the new document versions are
published, so you never have to discern which document is the newest version.
Paperless binders at a trial site are always up to date. This simplifies
CRA monitoring visits since there is no need to review a traditional paper
binder during their routine site visit.
#3 – Harmonize the document distribution process
The success of paper
processes is highly dependent on people to stay organized.
The standard operating procedure for one site could be vastly different at
other sites. Additionally, the sense of urgency to keep paper
processes moving along varies from site to site. When automated
processes are put in place, they keep things moving along according to
a unified process configured in the software system itself.
#4 – Speed up Study Start-up at every site
fact is, study documents are complicated. Paper complicates distribution
because paper moves slowly. And preparing a paper package requires meticulous
attention to detail, reviews by individuals, and finally some form of shipping
and receiving. For the study site, paper is received with all the other paper
that is used to run a business and is processed as time permits when patients
are not waiting in the lobby. But electronic study documents move at light
speed and are always in a highly organized state, dictated by the workflow of
the software system that moves the documents along. This shortens the time for
starting up the study at the sites, and site staff have more time to
focus on patient recruitment and care.
#5 – Decouple document collection
from site monitoring
paper documents, electronic document distribution and
collection is decoupled from site monitoring. Using an electronic
study document exchange system, the status of each document is
always known. There is no reason to call or visit the site to check the status
of a document or to make sure the site has filed all the paper artifacts
correctly. This saves time not only for
monitors, but also for the busy study site staff.
#6 – Find every document in one
world of paper is a complex set of processes and places. Most of these
processes have to do with moving the paper and most of the places are ad hoc repositories
(for example an email in-box), until eventually every paper document ends
up in the correct place. Electronic systems move the study
documents using workflows and keep every document in the
same repository while moving the document through each stage using distribution
requirements. This gives sponsors a huge cost savings while ensuring there is
only one record of truth pertaining to all regulatory study
#7 – Improve site satisfaction in a
By any measure, the elimination of paper at sites increases site satisfaction. Sites that use electronic systems provided by the sponsor or CRO never need to wonder what actions are needed by the sponsor, CRO or the site staff. Tasks are presented at the correct time and when action is required (like acknowledge or sign). Site staff is never asked to move regulatory documents from one place to another. They never need to print a document to sign it, and they never need to file a document since all of this happens automatically in an essential document shared system.
#8 – Reduce time required for Quality
a paperless system, documents are distributed, edited, and collected within the
system, creating an indisputable audit trail. The dates, times, user
identity, and various metadata of a document are recorded and updated
automatically. This removes a significant QA burden by
eliminating some QA checkpoints, and enables the quality assurance
staff to review and approve hundreds more documents each day.
#9 – Achieve a contemporaneous
The reason ICH introduced the concept of contemporaneousness is that in the past, many paper artifacts were found to contain curious details. For example, a signed document that shows the signer’s receipt date is later than the signers signature date. Paper-based processes are often paused for any number of reasons that have nothing to do with the clinical trial, leaving staff to try and catch up on work by signing with dates that “should” have been met. This can result in a sloppy TMF and could give regulatory inspectors a reason to look further into a trial’s accuracy.
#10 – Solve the completeness
biggest challenge to maintaining a state of completeness during a
study can be managing paper documents. Paper by its very nature is an
offline product that exists outside of the clinical trial itself. As the sites
get added to the trial or removed from the trial, the complexity of tracking
documents increases substantially. TMF managers even create “place holders” in
their eTMF for paper documents they expect to receive, and then run reports
showing the place holders so they can contact sites to request the missing
documents. In a properly designed electronic system, the expected
count of the study documents based on currently active sites is always known
along with the actual completion status of the document at any point in time.
The completeness challenge is solved because documents are never lost, delayed,
or missing. As soon as a document is signed, it appears in the QC work area,
ready for inclusion in your eTMF.
The transformation from a paper-based system to a paperless model in clinical trials is a goal at many clinical sponsors and research organizations. Connecting your eTMF to a clinical trial automation product is key to this transformation. The software product that helped achieve this goal at Novo Nordisk and Boehringer Ingelheim is the Study Collaboration Portal and can be further researched at www.innovocommerce.com